Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00078949
• Collaborator: (none)
• Enrollment: 849
• Locations: 27
• Arms: 4
• Actual Duration (Months): 183.8
• Patients Per Site: 31.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: cisplatin; Drug: cytarabine; Drug: dexamethasone; Drug: gemcitabine hydrochloride	Phase 3

Detailed Description

OBJECTIVES:

Salvage therapy

Primary

• Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab).

• To compare the transplantation rates of the two protocol salvage regimens.

Secondary

• Compare the event-free and overall survival of patients treated with these regimens.

• Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.

• Compare the quality of life of patients treated with these salvage regimens.

• Compare the toxic effects of these salvage regimens in these patients.

• Compare resource utilization for patients treated with these salvage regimens.

• Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.

Maintenance therapy

Primary

• Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment.

Secondary

• Compare the 2-year survival of patients treated with or without maintenance rituximab.

• Compare the toxic effects of rituximab vs observation alone in these patients.

OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs > 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (with or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab, cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response [CR] and CR unconfirmed [CRu] vs partial response [PR] vs stable disease [SD]), and prior rituximab (yes vs no).

• Salvage therapy: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.

• Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day

1. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day

In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator.

• ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.

• Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.

Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter.

PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.

Study Design

• Study Type: Interventional
• Actual Enrollment: 849 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin Compared To Dexamethasone, Cytarabine, And Cisplatin Plus/Minus Rituximab [(R)-GDP vs (R)-DHAP] As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkin's Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab vs Observation
• Actual Study Start Date: Aug 7, 2003
• Actual Primary Completion Date: Jul 29, 2013
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Salvage arm I Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8.	Drug: cisplatin; Given IV; Drug: dexamethasone; Given IV; Drug: gemcitabine hydrochloride; Given IV
Experimental: Salvage arm II Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2.	Drug: cisplatin; Given IV; Drug: cytarabine; Given IV; Drug: dexamethasone; Given IV
Experimental: Maintenance arm I Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.	Biological: rituximab; Given IV
No Intervention: Maintenance arm II Patients undergo observation only.

Outcome Measures

Primary Outcome Measures

1. Response Rate of Patients After 2 Courses of Chemotherapy [After 2 cycle of treatment]

   The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).

2. Transplantation Rate of Patients After 2 Courses of Chemotherapy [During period 1 (salvage chemotherapy)]

   Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients

3. Event-free Survival of Patients on Maintenance Randomization (Period 2) [during the period 2 (up to10 years)]

   Number of patients who develop EFS event during maintenance randomization (period 2)

Secondary Outcome Measures

1. Toxic Effect [48 months]

   Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:

• Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma)

• Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue [MALT] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse

• Must be histologically confirmed

• No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse

• Peripheral T-cell lymphoma

• Anaplastic large cell lymphoma

• Small noncleaved Burkitt-like lymphoma

• T-cell or B-cell lineage confirmed by immunohistochemistry

• Clinically or radiologically documented disease meeting either of the following criteria:

• Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI

• Lymph nodes must be > 1.5 cm by physical exam or CT scan

• Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI

• Bone lesions are not considered measurable

• Evaluable disease, defined as only nonmeasurable disease, including any of the following:

• Marrow infiltration

• Cytology-confirmed ascites or effusions

• Bony involvement

• Enlarged liver or spleen

• Unidimensionally measurable intrathoracic or abdominal masses

• Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine

• No uncontrolled CNS involvement by lymphoma

• No CNS disease at time of relapse

• CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained

PATIENT CHARACTERISTICS:

Age

• 16 to 65

Performance status

• ECOG 0-3

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,000/mm^3

• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)

• Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant cardiac dysfunction or cardiovascular disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Willing to complete quality of life questionnaires

• HIV negative

• No active, uncontrolled bacterial, fungal, or viral infection

• No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix

• No other concurrent serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy

• Prior rituximab allowed

Chemotherapy

• See Disease Characteristics

• At least 4 weeks since prior IV chemotherapy

• No prior high-dose chemotherapy with stem cell transplantation

Endocrine therapy

• No concurrent corticosteroids except for physiologic replacement

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

• Exceptions may be made for low-dose, non-myelosuppressive radiotherapy

• No prior radiotherapy to more than 25% of functioning bone marrow

• Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy

Surgery

• At least 2 weeks since prior major surgery

Other

• No other concurrent anticancer therapy

• No other concurrent experimental agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush-Presbyterian-St. Luke's Medical Centre	Chicago	Illinois	United States	60612
2	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
3	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
4	University of Cincinnati, Barrett Cancer Centre	Cincinnati	Ohio	United States	45219
5	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
6	The Queen Elizabeth Hospital	Woodville	South Australia	Australia	5011
7	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
8	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
9	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
10	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
11	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	AIB 3V6
12	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
13	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
14	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
15	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
16	Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
17	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario	Canada	P7B 6V4
18	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
19	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
20	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
21	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
22	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
23	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
24	CHA-Hopital Du St-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
25	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
26	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
27	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

• NCIC Clinical Trials Group

Investigators

• Study Chair: Michael R. Crump, MD, FRCPC, Princess Margaret Hospital, Canada
• Study Chair: Massimo Federico, MD, Azienda Ospedaliero-Universitaria di Modena

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00078949
• Other Study ID Numbers: LY12; CAN-NCIC-LY12; CDR0000353203; NCT00089817
• First Posted: Mar 9, 2004
• Last Update Posted: Apr 7, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by NCIC Clinical Trials Group: anaplastic large cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; angioimmunoblastic T-cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Gemcitabine; Cytarabine; Dexamethasone; Rituximab

Study Results

Participant Flow

Recruitment Details	619 patients in the first randomization. Only a selected subset of patient (N = 230) were randomized in period 2 of this study. Total sample size N = 849

Arm/Group Title	Salvage GDP	Salvage DHAP	Maintenance	Observation
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV	Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. rituximab: Given IV	Patients undergo observation only.
Period Title: Overall Study
STARTED	310	309	115	115
COMPLETED	306	304	112	112
NOT COMPLETED	4	5	3	3

Baseline Characteristics

Arm/Group Title	Salvage GDP	Salvage DHAP	Maintenance	Observation	Total
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV	Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. rituximab: Given IV	Patients undergo observation only.	Total of all reporting groups
Overall Participants	310	309	115	115	849
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55	55	54	55	55
Sex: Female, Male (Count of Participants)
Female	122 39.4%	118 38.2%	44 38.3%	48 41.7%	332 39.1%
Male	188 60.6%	191 61.8%	71 61.7%	67 58.3%	517 60.9%

Outcome Measures

1. Primary Outcome

Title	Response Rate of Patients After 2 Courses of Chemotherapy
Description	The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).
Time Frame	After 2 cycle of treatment

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Salvage GDP	Salvage DHAP
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV
Measure Participants	310	309
Number [percentage of response]	45.2	44.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Salvage GDP, Salvage DHAP
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The literature has suggested that the ORR is approximately 50% for this patient population treated with DHAP. The treatment difference is defined as the response rate for the DHAP arm minus that of GDP arm. We would consider GDP to be non-inferior to DHAP if we are 95% sure that the true difference is less than 10%. In order to rule out that the 10% difference with 80% power, we need to accrue a total of 630 eligible patients. The actual sample size for this final analysis is 619 patients.
Statistical Test of Hypothesis	p-Value	0.005
	Comments	p-value for non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -9.0 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Transplantation Rate of Patients After 2 Courses of Chemotherapy
Description	Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients
Time Frame	During period 1 (salvage chemotherapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salvage GDP	Salvage DHAP
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV
Measure Participants	310	309
Number [percentage of transplantation]	51.0	48.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Salvage GDP, Salvage DHAP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.1
	Confidence Interval	() 95%; -10.0 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Event-free Survival of Patients on Maintenance Randomization (Period 2)
Description	Number of patients who develop EFS event during maintenance randomization (period 2)
Time Frame	during the period 2 (up to10 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Maintenance	Observation
Arm/Group Description	Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. rituximab: Given IV	Patients undergo observation only.
Measure Participants	115	115
Number [participants]	53 17.1%	65 21%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Salvage GDP, Salvage DHAP
	Comments	It was estimated that 240 patients will be eligible for the maintenance question, and randomized with a 1:1 ratio to either rituximab or observation. It is expected that the 2-year event-free survival will be 50% on the observation arm. In order to detect a 15% difference in the 2-year event-free survival with an 80% power using a two-sided 5% level test, 142 events are required to detect an HR of 0.622.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Toxic Effect
Description	Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

All patients who received the protocol treatment.

Arm/Group Title	Salvage GDP	Salvage DHAP	Maintenance	Observation
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV	Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. rituximab: Given IV	Patients undergo observation only.
Measure Participants	306	304	112	112
Count of Participants [Participants]	36 11.6%	26 8.4%	16 13.9%	8 7%

Adverse Events

Time Frame	8.5 year
Adverse Event Reporting Description	Serious and Other Adverse Events were assessed in participants who received protocol treatment. All-cause mortality was collected for all enrolled participants
Arm/Group Title	Salvage GDP		Salvage DHAP		Maintenance		Observation
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. cisplatin: Given IV dexamethasone: Given IV gemcitabine hydrochloride: Given IV		Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. cisplatin: Given IV cytarabine: Given IV dexamethasone: Given IV		Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. rituximab: Given IV		Patients undergo observation only.
All Cause Mortality
	Salvage GDP		Salvage DHAP		Maintenance		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	177/310 (57.1%)		181/309 (58.6%)		39/115 (33.9%)		42/115 (36.5%)
Serious Adverse Events
	Salvage GDP		Salvage DHAP		Maintenance		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/306 (11.8%)		26/304 (8.6%)		16/112 (14.3%)		8/112 (7.1%)
Blood and lymphatic system disorders
Hemoglobin	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
DIC	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Febrile neutropenia	3/306 (1%)		11/304 (3.6%)		3/112 (2.7%)		1/112 (0.9%)
Cardiac disorders
Edema	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Ischemia/infarction	1/306 (0.3%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Pericardial effusion	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Sinus tachycardia	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Gastrointestinal disorders
Colitis	0/306 (0%)		2/304 (0.7%)		1/112 (0.9%)		1/112 (0.9%)
Constipation	0/306 (0%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Diarrhea	2/306 (0.7%)		2/304 (0.7%)		3/112 (2.7%)		0/112 (0%)
Dysphagia	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Nausea	4/306 (1.3%)		0/304 (0%)		2/112 (1.8%)		1/112 (0.9%)
Duodenal ulcer	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Gastric ulcer	1/306 (0.3%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Vomiting	2/306 (0.7%)		2/304 (0.7%)		2/112 (1.8%)		0/112 (0%)
Melena/GI bleeding	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Rectal bleeding	1/306 (0.3%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Hematemesis	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Abdominal pain	4/306 (1.3%)		2/304 (0.7%)		1/112 (0.9%)		1/112 (0.9%)
General disorders
Fatigue	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Pain-Other	2/306 (0.7%)		0/304 (0%)		1/112 (0.9%)		1/112 (0.9%)
Immune system disorders
Other	1/306 (0.3%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Other	3/306 (1%)		0/304 (0%)		0/112 (0%)		1/112 (0.9%)
Fever	3/306 (1%)		3/304 (1%)		2/112 (1.8%)		0/112 (0%)
Other	1/306 (0.3%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Other	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Infections and infestations
Wound-infectious	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Investigations
Granulocytes	2/306 (0.7%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Lymphopenia	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Platelets	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Leukocytes (total WBC)	1/306 (0.3%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Cardiac troponin T	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Creatinine	1/306 (0.3%)		2/304 (0.7%)		1/112 (0.9%)		0/112 (0%)
SGPT (ALT)	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
SGOT (AST)	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Bilirubin	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Weight loss	1/306 (0.3%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Metabolism and nutrition disorders
Dehydration	1/306 (0.3%)		1/304 (0.3%)		1/112 (0.9%)		0/112 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy	2/306 (0.7%)		4/304 (1.3%)		3/112 (2.7%)		3/112 (2.7%)
Nervous system disorders
Hemorrhage/bleeding	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Speech impairment	2/306 (0.7%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Neuropathy-sensory	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Syncope	1/306 (0.3%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Headache	1/306 (0.3%)		0/304 (0%)		1/112 (0.9%)		0/112 (0%)
Psychiatric disorders
Confusion	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Renal and urinary disorders
Renal failure	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Dysuria	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Hematuria	2/306 (0.7%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Respiratory, thoracic and mediastinal disorders
ARDS	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Cough	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Pleural effusion	1/306 (0.3%)		0/304 (0%)		0/112 (0%)		0/112 (0%)
Dyspnea	2/306 (0.7%)		3/304 (1%)		2/112 (1.8%)		0/112 (0%)
Vascular disorders
Hypertension	0/306 (0%)		1/304 (0.3%)		0/112 (0%)		0/112 (0%)
Hypotension	1/306 (0.3%)		1/304 (0.3%)		1/112 (0.9%)		0/112 (0%)
Thrombosis/embolism	5/306 (1.6%)		2/304 (0.7%)		3/112 (2.7%)		1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	Salvage GDP		Salvage DHAP		Maintenance		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	287/306 (93.8%)		293/304 (96.4%)		98/112 (87.5%)		90/112 (80.4%)
Blood and lymphatic system disorders
Febrile neutropenia	28/306 (9.2%)		71/304 (23.4%)		10/112 (8.9%)		3/112 (2.7%)
Cardiac disorders
Edema	39/306 (12.7%)		64/304 (21.1%)		8/112 (7.1%)		9/112 (8%)
Ear and labyrinth disorders
Inner ear/hearing	50/306 (16.3%)		76/304 (25%)		14/112 (12.5%)		12/112 (10.7%)
Eye disorders
Blurred vision	21/306 (6.9%)		15/304 (4.9%)		5/112 (4.5%)		3/112 (2.7%)
Gastrointestinal disorders
Constipation	133/306 (43.5%)		113/304 (37.2%)		10/112 (8.9%)		14/112 (12.5%)
Diarrhea	64/306 (20.9%)		85/304 (28%)		19/112 (17%)		11/112 (9.8%)
Dysphagia	17/306 (5.6%)		17/304 (5.6%)		12/112 (10.7%)		3/112 (2.7%)
Dyspepsia/heartburn	59/306 (19.3%)		51/304 (16.8%)		17/112 (15.2%)		10/112 (8.9%)
Nausea	172/306 (56.2%)		221/304 (72.7%)		22/112 (19.6%)		14/112 (12.5%)
Stomatitis	61/306 (19.9%)		70/304 (23%)		7/112 (6.3%)		2/112 (1.8%)
Vomiting	95/306 (31%)		151/304 (49.7%)		18/112 (16.1%)		8/112 (7.1%)
Other	4/306 (1.3%)		6/304 (2%)		8/112 (7.1%)		0/112 (0%)
Abdominal pain	65/306 (21.2%)		47/304 (15.5%)		22/112 (19.6%)		14/112 (12.5%)
General disorders
Fatigue	225/306 (73.5%)		201/304 (66.1%)		65/112 (58%)		59/112 (52.7%)
Rigors, chills	10/306 (3.3%)		21/304 (6.9%)		6/112 (5.4%)		5/112 (4.5%)
Chest pain	19/306 (6.2%)		27/304 (8.9%)		5/112 (4.5%)		7/112 (6.3%)
Pain-Other	21/306 (6.9%)		23/304 (7.6%)		10/112 (8.9%)		4/112 (3.6%)
Immune system disorders
Fever	45/306 (14.7%)		74/304 (24.3%)		14/112 (12.5%)		12/112 (10.7%)
Infections and infestations
Infection w/o neutropen	64/306 (20.9%)		58/304 (19.1%)		50/112 (44.6%)		39/112 (34.8%)
Investigations
Weight loss	18/306 (5.9%)		15/304 (4.9%)		12/112 (10.7%)		7/112 (6.3%)
Metabolism and nutrition disorders
Anorexia	77/306 (25.2%)		94/304 (30.9%)		17/112 (15.2%)		16/112 (14.3%)
Dehydration	17/306 (5.6%)		22/304 (7.2%)		3/112 (2.7%)		1/112 (0.9%)
Hypomagnesemia	6/306 (2%)		18/304 (5.9%)		3/112 (2.7%)		2/112 (1.8%)
Musculoskeletal and connective tissue disorders
Muscle weakness	23/306 (7.5%)		20/304 (6.6%)		6/112 (5.4%)		9/112 (8%)
Arthralgia	28/306 (9.2%)		15/304 (4.9%)		20/112 (17.9%)		17/112 (15.2%)
Myalgia	49/306 (16%)		42/304 (13.8%)		25/112 (22.3%)		24/112 (21.4%)
Bone pain	33/306 (10.8%)		32/304 (10.5%)		17/112 (15.2%)		17/112 (15.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	46/306 (15%)		41/304 (13.5%)		6/112 (5.4%)		2/112 (1.8%)
Nervous system disorders
Taste disturbance	28/306 (9.2%)		43/304 (14.1%)		10/112 (8.9%)		11/112 (9.8%)
Dizziness	39/306 (12.7%)		33/304 (10.9%)		12/112 (10.7%)		5/112 (4.5%)
Neuropathy-motor	30/306 (9.8%)		13/304 (4.3%)		5/112 (4.5%)		3/112 (2.7%)
Neuropathy-sensory	106/306 (34.6%)		74/304 (24.3%)		25/112 (22.3%)		28/112 (25%)
Syncope	7/306 (2.3%)		16/304 (5.3%)		0/112 (0%)		1/112 (0.9%)
Headache	59/306 (19.3%)		72/304 (23.7%)		10/112 (8.9%)		6/112 (5.4%)
Neuropathic pain	7/306 (2.3%)		9/304 (3%)		9/112 (8%)		8/112 (7.1%)
Psychiatric disorders
Anxiety	40/306 (13.1%)		30/304 (9.9%)		10/112 (8.9%)		8/112 (7.1%)
Insomnia	61/306 (19.9%)		54/304 (17.8%)		13/112 (11.6%)		10/112 (8.9%)
Depression	20/306 (6.5%)		13/304 (4.3%)		7/112 (6.3%)		7/112 (6.3%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	8/306 (2.6%)		9/304 (3%)		10/112 (8.9%)		8/112 (7.1%)
Epistaxis	20/306 (6.5%)		16/304 (5.3%)		0/112 (0%)		0/112 (0%)
Cough	55/306 (18%)		61/304 (20.1%)		38/112 (33.9%)		19/112 (17%)
Hiccoughs	18/306 (5.9%)		17/304 (5.6%)		0/112 (0%)		0/112 (0%)
Dyspnea	65/306 (21.2%)		69/304 (22.7%)		19/112 (17%)		24/112 (21.4%)
Skin and subcutaneous tissue disorders
Sweating	51/306 (16.7%)		33/304 (10.9%)		13/112 (11.6%)		12/112 (10.7%)
Alopecia	31/306 (10.1%)		42/304 (13.8%)		13/112 (11.6%)		10/112 (8.9%)
Dry skin	3/306 (1%)		14/304 (4.6%)		7/112 (6.3%)		5/112 (4.5%)
Rash/desquamation	61/306 (19.9%)		38/304 (12.5%)		10/112 (8.9%)		15/112 (13.4%)
Other	7/306 (2.3%)		6/304 (2%)		6/112 (5.4%)		4/112 (3.6%)
Vascular disorders
Hypotension	14/306 (4.6%)		25/304 (8.2%)		4/112 (3.6%)		1/112 (0.9%)
Thrombosis/embolism	24/306 (7.8%)		24/304 (7.9%)		4/112 (3.6%)		3/112 (2.7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.